Inhibition of nuclear transcription factor-κB and activation of peroxisome proliferator-activated receptors in HepG2 cells by cucurbitane-type triterpene glycosides from Momordica charantia

J Med Food. 2012 Apr;15(4):369-77. doi: 10.1089/jmf.2011.1766. Epub 2012 Jan 16.

Abstract

Momordica charantia is used to treat various diseases, including inflammatory conditions. Previous reports indicated that the extract of this plant inhibits activation of nuclear transcription factor-κB (NF-κB) but activates peroxisome proliferator-activated receptor (PPAR). Additionally, cucurbitane-type triterpene glycosides are the main bioactive components of the fruit of M. charantia. Therefore, we investigated the anti-inflammatory activity of 17 cucurbitane-type triterpene glycosides (1-17) isolated from this plant. Their inhibition of NF-κB and activation of PPAR activities in HepG2 cells were measured using luciferase reporter and PPAR subtype transactivation assays. Compounds 6 and 8 were found to inhibit NF-κB activation stimulated by tumor necrosis factor-α (TNFα) in a dose-dependent manner. With 50% inhibition concentration (IC(50)) values of 0.4 μM, compounds 6 and 8 were more potent inhibitors than the positive control, sulfasalazine (IC(50)=0.9 μM). Compounds 4, 6, and 8 also inhibited TNFα-induced expressions of inducible nitric oxide synthase and cyclooxygenase-2 mRNA. However, only compound 13 significantly increased PPARγ transactivation.

Publication types

  • Research Support, Non-U.S. Gov't

MeSH terms

  • Anti-Inflammatory Agents / pharmacology*
  • Cyclooxygenase 2 / genetics
  • Cyclooxygenase 2 / metabolism
  • Gene Expression Regulation / drug effects
  • Glycosides / pharmacology*
  • Hep G2 Cells
  • Humans
  • Inhibitory Concentration 50
  • Luciferases / metabolism
  • Momordica charantia / chemistry*
  • NF-kappa B / antagonists & inhibitors*
  • NF-kappa B / metabolism
  • Nitric Oxide Synthase Type II / genetics
  • Nitric Oxide Synthase Type II / metabolism
  • PPAR gamma / metabolism
  • Peroxisome Proliferator-Activated Receptors / metabolism*
  • Plant Extracts / pharmacology*
  • RNA, Messenger / metabolism
  • Triterpenes / pharmacology*
  • Tumor Necrosis Factor-alpha / antagonists & inhibitors
  • Tumor Necrosis Factor-alpha / metabolism

Substances

  • Anti-Inflammatory Agents
  • Glycosides
  • NF-kappa B
  • PPAR gamma
  • Peroxisome Proliferator-Activated Receptors
  • Plant Extracts
  • RNA, Messenger
  • Triterpenes
  • Tumor Necrosis Factor-alpha
  • cucurbitane
  • Luciferases
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • PTGS2 protein, human